The proposed research concerns the synthesis of several classes of compounds that have been shown to possess very important physiological activity. Included are some highly promising anti-cancer agents, antibiotics, and other useful drugs. The development of synthetic methods for preparing these compounds is vitally important in health-related studies of the materials. The proposed syntheses will provide new sources that will be independent of the limited natural supplies of these compounds. Therefore, the greater availability of these compounds will permit further detailed biomedical investigations of their applications as drugs for treatment of major human diseases. This proposal specifically discusses new methods for the synthesis of three general classes of physiologically active compounds: alpha-pyrones, cycloalken-3-ones, and acrylte-containing systems. In the broadest sense, the last class includes simple substituted acrylates, enals, hydroxyenals, alpha-methyiene lactones, and more complex acrylate systems. All three classes of compounds are related as alpha, beta-unsaturated carconyl compounds. Generally, their basis of activity is that they serve as very reactive Michael acceptors of sulfhydryl groups and thus interfere with biological processes that are controlled by thiol-containing enzymes. Several of the members of these classes are especially attractive research objectives because of the very potent anticancer activity that they have exhibited. The proposed methods for all three classes of compounds involve the use of novel chemical intermediates such as new dianions that may be useful in the synthesis of many other types of important compouns as well. One of the approaches to the cycloalkenones will be applicable to the construction of the D-ring of steroids such as the estrogens.